User:Jaime Prilusky/Sandbox One Applet



Hemoglobin is an oxygen-transport protein. Hemoglobin is an allosteric protein. It is a tetramer composed of two types of subunits designated α and β, with stoichiometry α2β2. The four subunits of hemoglobin sit roughly at the corners of a tetrahedron, facing each other across a cavity at the center of the molecule. Each of the subunits contains a heme prosthetic group. The heme molecules give hemoglobin its red color.

Each individual heme molecule contains one Fe2+ atom. In the lungs, where oxygen is abundant, an oxygen molecule binds to the ferrous iron atom of the heme molecule and is later released in tissues needing oxygen. The heme group binds oxygen while still attached to the hemoglobin monomer. The spacefill view of the hemoglobin polypeptide subunit with an oxygenated heme group shows how the oxygenated heme group is held within the polypeptide.

Anchoring of the heme is facilitated by a histidine nitrogen that binds to the iron. A second histidine is near the bound oxygen. The "arms" (propanoate groups) of the heme are hydrophilic and face the surface of the protein while the hydrophobic portions of the heme are buried among the hydrophobic amino acids of the protein.

Perhaps the most well-known disease caused by a mutation in the hemoglobin protein is sickle-cell anemia. It results from a mutation of the sixth residue in the β hemoglobin monomer from glutamic acid to a valine. This hemoglobin variant is termed 'hemoglobin S' (2hbs).

Hemoglobin subunit binding O2
For hemoglobin, its function as an oxygen-carrier in the blood is fundamentally linked to the equilibrium between the two main states of its quaternary structure, the unliganded "deoxy" or "T state" versus the liganded "oxy" or "R state". The unliganded (deoxy) form is called the "T" (for "tense") state because it contains extra stabilizing interactions between the subunits. In the high-affinity R-state conformation the interactions which oppose oxygen binding and stabilize the tetramer are somewhat weaker or "relaxed". In some organisms this difference is so pronounced that their Hb molecules dissociate into dimers in the oxygenated form. Structural changes that occur during this transition can illuminate how such changes result in important functional properties, such as cooperativity of oxygen binding and allosteric control by pH and anions. Hemoglobin is definitely not a pure two-state system, but the T to R transition provides the major, first-level explanation of its function.

The hemoglobin molecule (or "Hb") is a tetramer of two α and two β chains, of 141 and 146 residues in human. They are different but homologous, with a "globin fold" structure similar to myoglobin.

Here we see a single α chain of hemoglobin, starting with an overview of the subunit. The 6 major and 2 short α-helices that make up the structure of a Hb subunit (the "globin fold") are labeled A through H, which is the traditional naming scheme. For example, the proximal histidine (the tightest protein Fe ligand) is often called His F9, since it is residue 9 on helix F (it is residue 87 in the human α chain). The helices form an approximately-cylindrical bundle, with the heme and its central Fe atom bound in a <scene name='Hemoglobin/3hhb_chaina_efpocket/4'>hydrophobic pocket between the E and F helices.